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Phenylalanine hydroxylase deficiency is a treatable inherited disease in which the body cannot properly process the amino acid phenylalanine due to a deficient enzyme called phenylalanine hydroxylase. If severe forms of the disease go untreated, the buildup of phenylalanine can be toxic to the brain, causing impaired development and leading to severe and irreversible mental disability. If treated early and consistently however, people with phenylalanine hydroxylase deficiency can lead completely normal lives.
The disease can be divided into several categories based on the amount of enzyme deficiency: Classic phenylketonuria (PKU), variant PKU, and non-PKU hyperphenylalaninemia (non-PKU HPA). Since the mid-1960s, it has been standard for hospitals in North America to screen newborns for phenylalanine hydroxylase deficiency using a drop of blood obtained from a heel prick. This is now a routine practice in most developed countries.
It can be difficult to predict how severely affected a child will be based on the particular genetic mutations they carry. Children with any form phenylalanine hydroxylase deficiency should be evaluated by a specialist immediately after birth.
Classic PKU is the most common and severe form, resulting from an absence or near absence of the phenylalanine hydroxylase enzyme.
If PKU is not promptly diagnosed and treated with a special diet, mental disability will occur, along with a number of other symptoms including a small head, seizures, behavior problems, a "mousy" or "musty" odor, abnormal gait, low bone density, and eczema (a skin condition). These are all avoidable if the proper diet is instituted shortly after birth.
Variant PKU is an intermediate form of the disease, less severe than classic PKU but more severe than non-PKU HPA. A child with variant PKU is at risk for developing the symptoms associated with classic PKU. Though the symptoms may be milder, there is still a risk for impaired mental development if the child's intake of phenylalanine is not monitored.
Non-PKU HPA is the mildest form of phenylalanine hydroxylase deficiency. People with non-PKU HPA have a higher level of phenylalanine hydroxylase than do people with classic or variant PKU and are consequently at lower risk for developing brain damage. Some people with non-PKU HPA are able to tolerate a normal diet and do not require treatment. This will vary from person to person and must be determined by a medical professional based on the levels of phenylalanine in the person’s blood.
The frequency of carriers and affected individuals in select populations is listed below.
|Ethnic Group||Carrier Rate||Affected Rate|
|Turkish||1 in 26||1 in 2,600|
|Irish||1 in 33||1 in 4,500|
|Caucasian American||1 in 50||1 in 10,000|
|East Asian||1 in 51||1 in 10,000|
|Finnish||1 in 200||1 in 160,000|
|Japanese||1 in 200||1 in 160,000|
|Ashkenazi Jewish||1 in 225||1 in 200,000|
The degree of enzyme deficiency varies among people with phenylalanine hydroxylase deficiency, and therefore the treatment must also be individualized based on the levels of phenylalanine in the blood. An infant with any form of phenylalanine hydroxylase deficiency should be evaluated immediately after birth to determine whether or not he or she requires treatment. A blood test can reveal the amount of functioning phenylalanine hydroxylase in the body and this will indicate the amount of phenylalanine the person can safely consume.
While people with classic PKU must adhere to a strict low-phenylalanine diet, others with milder form of the disease are able to safely consume small amounts of the amino acid. For people with non-PKU HPA, treatment may not even be necessary.
Generally speaking, a diet low in protein and free from phenylalanine is important in preserving mental function in a person with classic PKU. Phenylalanine-free formulas are available for infants. Maintaining appropriate levels of phenylalanine in the brain can be achieved through blood testing and diet adjustment. This must be closely supervised by medical professionals. In most cases, this special diet must be maintained for life.
People with any form of phenylalanine hydroxylase deficiency should be conscious to avoid consuming aspartame, an artificial sweetener that contains phenylalanine.
Women with phenylalanine hydroxylase deficiency who become pregnant must be particularly careful to maintain safe levels of phenylalanine in their own bodies in order to avoid birth defects in their children. Ideally this begins prior to conception.
In late 2007, the medication sapropterin dihydrochloride (brand name: Kuvan) was approved by the FDA for use in people with phenylalanine hydroxylase deficiency. In some, it can enhance the activity of the deficient enzyme and lower levels of phenylalanine in the body, allowing for a relaxation of the dietary restrictions. Some people with the disease do not respond to the drug, however. The people who do respond to this treatment usually have milder forms of the disease.
If a person with classic or variant PKU is treated early and consistently for the disease, the prognosis can be excellent. Many people with PKU have gone on to lead normal lives with normal intelligence and lifespan. If treatment is not begun early or adequately maintained, a person with a more severe form of PKU is at risk for severe and irreversible brain damage.
The prognosis is good for a person with non-PKU HPA. He or she may lead a normal life without treatment.
A non-profit group focused on educating the public about PKU and supporting children with the disease..
3790 Via De La Valle, Suite 120
Del Mar, CA 92014
Phone: (800) 377-6677
Secondary Phone: (858) 509-0767
Explanations of an extensive number of genetic diseases written for everyday people by the U.S. government's National Institutes of Health..
A fact sheet on PKU from the nation's leading non-profit dedicated to improving the health of babies by reducing birth defects, premature birth, and infant mortality..
1275 Mamaroneck Avenue
White Plains, NY 10605
Phone: (914) 997-4488 (national office)
A division of the National Institutes of Health which is well-known for having mapped the human genome. This page on PKU has information about the disease as well as links to numerous other PKU-related organizations.